Dimethyl (diazomethyl)phosphonate → 2-(3-(3-Fluoro-4-prop-1-ynyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl)-isoindole-1,3-dione

Participants

Reaction Conditions

Reaction Steps

To a −78° C. solution of potassium t-butoxide (17 mL of a 1.0 M solution in THF) was added a −78° C. THF (4 mL) solution of dimethyl diazomethylphosphonate (2.53 g, prepared according to the procedure described in J. Org. Chem. 1971, 36, 1379-1385). The mixture was stirred at −78° C. for 10 minutes then a −78° C. solution of Example 3A (5.19 g) in THF (100 mL) was added via cannula over 20 minutes. The reaction mixture was stirred for 24 hours, gradually warming to room temperature. The mixture was quenched with 1:1 saturated ammonium chloride/water (200 mL) and extracted with dichloromethane (50 mL). The aqueous layer was extracted with 4:1 THF/dichloromethane (250 mL), and the combined extracts were washed with 1:1 saturated sodium bicarbonate/water (200 mL) and 1:1 brine/water (200 mL). The organic extracts were dried over MgSO4, filtered, and concentrated to provide crude product. The crude product was purified by flash column chromatography on silica gel eluting with 4:1 hexanes/acetone to provide the desired product. MS (ESI(+)) m/e 379 (M+H)+; 1H NMR (300 MHz, CDCl3) δ 7.9 (m, 2H), 7.77 (m, 2H), 7.45 (dd, J=2.4, 9 Hz, 1H), 7.36 (d, J=7.2 Hz, 1H), 7.25-7.35 (dd, J=2.4, 8.7 Hz, 1H), 4.97 (m, 1H), 4.07-4.18 (m, 2H), 3.8-4.01 (m, 2H), 2.09 (s, 3H).

Provenance & Evidence